1. Field of the Invention
The invention relates to a composition containing rutin and ascorbic acid derivatives as well as methods for depigmenting skin, preventing or combating skin blemishes and preventing or combating ageing of skin. This composition may be applied to the face, body, neck, hands or legs.
2. Description of the Background
Over the course of time, various signs appear on the skin which are very characteristic of ageing. In particular, the structure and functions of the skin are modified. This ageing is physiological in nature but may also be photoinduced due to repeated exposure of the skin to sunlight, in particular ultraviolet light.
The action of this light on the constituents of the skin and on the sebum secreted by the skin leads to the formation of oxygen-containing free radicals. These radicals cause considerable damage in cell membranes (permeability of the membranes), cell nuclei (mutation by action on RNA or DNA) and tissues (necroses, degeneration). Thus, the skin should be protected against these free radicals.
The main clinical signs of ageing of the skin are the appearance of fine lines and deep wrinkles which increase with age, as well as a disorganization of the "grain" of the skin (i.e., the skin microrelief is less uniform and is anisotropic in nature). Moreover, the skin complexion is generally modified and appears yellowed, which essentially is due to a disorganization of the microcirculation (less haemoglobin in the papillary dermis). Furthermore, many colored and/or darker marks appear at the skin surface and, in particular, on the hands, imparting non-uniformity to the skin. In general, these marks are due to an appreciable production of melanin in the skin epidermis and dermis. In certain cases of intense exposure to solar rays, these marks may become cancerous. Moreover, diffuse irritations and occasionally telangiectasias may exist on certain areas of the skin.
Another clinical sign of ageing is the dry and rough appearance of the skin, which is due essentially to pronounced desquamation caused by diffracting light rays. These squama also contribute towards the somewhat grayish appearance of the complexion. Thus, the clinical signs of skin ageing result essentially from dysfunction of the main biological mechanisms involved in the skin.
Also, certain people with colored skin seek to reduce their color by using depigmenting and/or anti-pigmenting agents.
Thus, a composition which is capable of preventing and/or combating the onset of ageing and the existing signs of ageing, more especially photoinduced ageing, such as wrinkles and fine lines, which is capable of depigmenting the skin and of preventing and/or combating skin pigmentation marks irrespective of their origin, and which is capable of protecting the skin in particular by suppression of the formation of oxygen-containing free radicals is desirable.
One of the effective known means for combating premature ageing of the skin consists in supplying the skin with molecules capable of helping the cells defend themselves against the excess of photoinduced free radicals. Molecules having a hydrophilic, strong reductive power which react with free radicals such as peroxide, superoxide and hydroxyl radicals are especially useful.
One of these molecules capable of effectively combating these free radicals and thus of strengthening the defenses of skin tissue against external attack (ultraviolet radiation, pollution) is ascorbic acid, or vitamin C, on account of its antioxidant properties. This compound also compensates for the deficiency of vitamin E, by stimulating the synthesis of connective tissue and, in particular, skin collagen, and depigmenting the skin.
Unfortunately, on account of its chemical structure and its reductive properties, ascorbic acid is very sensitive to certain environmental parameters such as light, oxygen and water (owing to its pH and the presence of traces of metals). As the rapid degradation of ascorbic acid ensues, it loses its properties, counteracting the desired effect. This degradation results in a yellow/brown color in the composition containing it.
In order to reduce and delay the degradation of ascorbic acid, researchers have attempted to block the reactive site of ascorbic acid, namely the hydroxyl site, by esterification with a saccharide. For example, ascorbyl-2-glucoside is described in document EP-A-487,404 and has the advantages of being more stable than vitamin C, having good water solubility and being bioconvertible into vitamin C on the skin by means of certain skin enzymes, thereby allowing all the properties of vitamin C to be regained.
On account of its good water solubility, this compound may be incorporated into a large number of excipients. However, its stability in an aqueous medium, and in particular in an oil-in-water emulsion, is good (longer than 14 days) only if the pH was above 6. However, the stability of cosmetic compositions at room temperature must be longer than several months, in particular since no expiration date for the products is indicated on the packaging.
The following table shows the stability of 2-ascorbyl glucoside over time and as a function of the pH.
TABLE ______________________________________ 14 days without 14 days 30 days 60 days Storage Stability Day 0 light in light in light in light ______________________________________ pH of the aqueous solu- 2.2 2.18 2.27 2.1 2.48 tion % residual ascorbyl-2- 12.3% 11.8% 11.6% 10.4% 9.3% glucoside Stability (residual %/ 100% 95.9% 94.3% 84.5% 75.6% initial %) pH of the aqueous solu- 2.7 2.7 2.8 2.59 2.59 tion % residual ascorbyl-2- 0.58% 0.57% 0.57% 0.51% 0.47% glucoside Stability (residual %/ 100% 98.3% 98.3% 87.9% 81% initial %) pH (citrate/phosphate 4 3.98 3.78 3.74 3.86 buffer) % residual ascorbyl-2- 0.6% 0.6% 0.58% 0.54% 0.49% glucaside Stability (residual %/ 100% 100% 96.7% 90% 81.7% initial %) pH (citrate/phosphate 6 6.04 5.96 5.91 6.21 buffer) % residual ascorbyl-2- 0.59% 0.61% 0.6% 0.61% 0.59% glucoside Stability (residual %/ 100% 103.4% 101.7% 103.4% 100% initial %) pH (borate buffer) 8 7.9 7.53 7.54 7.79 % residual ascorbyl-2- 0.61% 0.62% 0.62% 0.61% 0.59% glucoside Stability (residual %/ 100% 101.6% 101.6% 100% 96.7% initial %) ______________________________________
From this table, it is clear that the stability of 2-ascorbyl glucoside is enhanced when the pH is above 6. This stability at pH&gt;6 holds true for other saccharide esters of ascorbic acid.
Other molecules with antioxidant properties which are known are flavonoids. These compounds have the advantage of being anti-inflammatory agents as well as anti-superoxide anion agents. More generally, they are effective in deactivating radical species of oxygen. These properties are described in documents U.S. Pat. No. 5,043,323, U.S. Pat. No. 5,443,839, U.S. Pat. No. 4,814,346, JP-A-01096125, JP-A-01096126 and in the articles "Flavonoids as antioxidants evaluated by in vitro and in situ liver chemiluminescence" by C. G. Fraga et al., Biochemical Pharmacology, vol. 36, No. 5, 1987, pp. 717-720; "Flavonoids as anti-inflammatory agents" by M. J. Alcaraz and M. J. Jimenez, Fitoterapia, vol. LIX, No. 1, 1988, pp. 25-38; and "Flavonoids are scavengers of superoxide anions" by J. Robak and R. J. Gryglewski, Biochemical Pharmacology, vol. 37, No. 5, 1988, pp. 837-841; all incorporated herein by reference.
Unfortunately, most of these flavonoids are sensitizing compounds which can cause allergic reactions when they are applied to the skin. In contrast, rutin is a flavonoid which has a zero score in the FCA method (maximized test with Freud adjuvant, as described in the article "Aspects of the relationships between chemical structure and sensitizing potency of flavonoids and related compounds" by H. W. Schmalle et al., Prog. Clin. Biol. Res., vol. 213, 1986, pp. 387-390). Unfortunately, rutin is very sparingly water-soluble (about 0.01%).
In contrast, saccharide esters of rutin such as alpha-glycosyl rutin are water soluble and, in addition, are bioconvertible on contact with skin enzymes and have better light stability than rutin. However, alpha-glycosyl rutin gives a yellow solution in water; the intensity of the color depends on the pH. If the pH is below or equal to 5, the yellow color is of weak intensity, from virtually colorless to pale yellow, and is stable over time. If the pH is above 5, the color becomes increasingly intense and ranges from dark yellow to brown depending on the percentage of alpha-glucosyl rutin. In this case, the composition becomes cosmetically unacceptable, not only due to its color but also because the color changes over time.
In other words, ascorbyl-2-glucoside and, more generally, saccharide esters of ascorbic acid are unstable at pH values below 5. Alpha-glycosyl rutin and, more generally, saccharide esters of rutin color excipients containing them at pH values above 5 in such a manner as to make them unacceptable.